Abstract

Background

The standard treatment for patients with chronic hepatitis C (CHC), pegylated interferon-α
(PEG-IFN) plus ribavirin (RBV) does not provide a sustained virological response (SVR)
in all patients. Genetic variations at the interleukin 28B (IL-28B) locus are important
in predicting outcome following therapy in CHC patients.

Results

We investigated the role of IL28B variations (rs8099917) in response to PEG-IFN-α/RBV
treatment and evaluated its association with the risk of the null virological response (NVR) and
relapse (REL) in different viral genotypes. We found that the overall distributions
of the genotype among the SVR, NVR, and REL groups were significantly different (P<0.001).
Patients with the TG genotype had an increased risk of NVR and REL (OR=6.45 95% CI
=2.88–14.47, P<0.001 for NVR; OR=2.51, 95% CI =1.29–4.86, P=0.006 for REL, respectively),
and patients with the GG genotype had a further increased risk of NVR and REL (OR=12.04,
95% CI =3.21–45.13, P<0.001 for NVR; ,OR=4.30, 95% CI =1.21–15.13, P=0.017 for REL,
respectively). G variant genotypes (TG+GG) also had an increased risk of NVR and REL,
and there was a significant trend for a dose-effect of G allele on the risk of NVR
and REL (P<0.05). The SVR rate in TT higher than in TG+GG was more pronounced in those
patients infected with non-G1 compared to the patients infected with G1. The treatment
response did differ based on the rs8099917 genotype in patients with different viral
genotypes, compared with patients infected with the non-G1, the G1 infected patients
had an increased risk of NVR and REL (OR=2.03 95% CI =1.03–4.01, P=0.04 for NVR and
OR=2.58, 95% CI =1.35–4.94, P=0.004 for REL, respectively). Moreover, multivariate
regression analysis show that the rs8099917 G allele was the only independent factor
significantly associated with a NVR and REL.

Conclusion

This study suggests that host genetic polymorphisms rs8099917 in the vicinity of IL-28B
is the most important predictor of treatment response of PEG-IFN-α/RBV for HCV patients
in China.